title: Detection of altered adhesion molecule expression in experimental tumors by a radiolabeled monoclonal antibody.
abstract: Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin alpha 3 can be detected by a radiolabeled monoclonal antibody. The in vitro binding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin alpha 3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with 125I- and 111In-labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin alpha 3 was expressed in various kinds of tumors and could be localized by the radiolabeled antibody, and 2) the expression of integrin alpha 3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin alpha 3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with alpha or beta emitters.
authors.affiliation: Department of Nuclear Medicine, Faculty of Medicine, Kyoto University.
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: H
authors.initials: H
authors.lastname: Sakahara
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Hattori
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: S
authors.initials: S
authors.lastname: Miyatake
authors.forename: Y
authors.initials: Y
authors.lastname: Namba
authors.forename: J
authors.initials: J
authors.lastname: Konishi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D006801:Humans; D039422:Integrin alpha3; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D011863:Radioimmunoassay; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D039422:Integrin alpha3; D016023:Integrins; D009363:Neoplasm Proteins